Dr Morgans on the Relationship Between PSA Levels and Radiographic Progression in nmCRPC

Alicia Morgans, MD, MPH, genitourinary medical oncologist, medical director, Survivorship Program, Dana-Farber Cancer Institute; associate professor, medicine, Harvard Medical School, discusses the relationship between prostate-specific antigen (PSA) levels and the risk of radiologic progression in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), as evaluated in the follow-up analysis of the phase 3 ARAMIS trial (NCT02200614).

The ARAMIS trial evaluated patients with nmCRPC who received androgen deprivation therapy (ADT) combined with either darolutamide (Nubeqa) or placebo, Morgans begins. PSA levels were measured, and conventional imaging was conducted every 16 weeks. The cumulative incidence of time to radiologic progression was compared between patients with PSA levels less than 0.2 ng/mL–the international standard for undetectable PSA–and those with higher PSA levels. For patients who experienced radiological progression, their PSA levels at the time of progression were also evaluated.

The results demonstrated that a significantly higher proportion of patients treated with darolutamide achieved PSA levels less than 0.2 ng/mL compared with those who received ADT alone, Morgans reports. This intensified therapy with darolutamide resulted in more effective disease control, allowing more patients to reach this critical PSA threshold, she says. The study further revealed that patients who achieved PSA levels less than 0.2 ng/mL had an extremely low rate of metastasis during follow-up. By 3 years, only 8.7% of these patients experienced metastasis, Morgans states. In contrast, patients who did not achieve this low PSA level had a significantly higher rate of progression or metastasis, with approximately half of patients experiencing such events by 36 months, she details.

These findings underscore a clear dichotomy in clinical outcomes between patients who achieve a deep PSA response and those who do not, Morgans says. This highlights the importance of achieving and maintaining low PSA levels for improving long-term outcomes, she emphasizes. Additionally, it was evident that treatment with darolutamide led to more patients attaining a deep and durable PSA response compared with ADT alone, Morgans notes. This is clinically significant as it suggests that darolutamide can provide substantial benefits in terms of delaying disease progression and reducing the risk of metastasis, ultimately leading to better patient outcomes, Morgans concludes.